Cerebral Vascular Reserve in Small Vessel Disease and Alzheimers Disease

Alzheimers disease and cerebral small vessel disease have a considerably overlap in patients and have common risk factors. The diseases are difficult to separate in individual patients and we hypothesize that a reduced cerebral vascular reserve may be a measurement of small vessel disease independent of Alzheimers disease.

Patients with presumed Alzheimers disease (n=20), cerebral small vessel disease (n=20) and healthy age-matched subjects (n=15) are examined with quantitative [15O]H2O positron emission tomography (PET) for measurements of brain perfusion before and after diamox infusion that dilates cerebral vessels. Additional [15O]H2O PET scans of the heart allows for a non-invasive input function so the cerebral vascular reserve can be measured quantitatively.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Dementia, Vascular
• Intervention / Treatment: Diagnostic test: Cerebral [15O]H2O PET before and after diamox infusion

Detailed Description

Alzheimers disease and cerebral small vessel disease are increasingly common in the elderly population and constitute around 90% of new dementia cases in Denmark. The diseases have a considerably overlap in patients and have common risk factors. The cause of dementia can be difficult to separate in individual patients but a reduced cerebral vascular reserve may be a measurement of small vessel disease independent of Alzheimers disease. We hypothesized that patient with small vessel disease have reduced increase in brain perfusion after medical brain vessel dilatation. While Alzheimer patients may have reduced perfusion in rest but normal increase after medical brain vessel dilatation as compared to healthy subjects.

Patients with presumed Alzheimers disease (n=20), cerebral small vessel disease (n=20) and healthy age-matched subjects (n=15) are examined with quantitative [15O]H2O PET for measurements of brain perfusion before and after diamox infusion that dilates cerebral vessels. Additional [15O]H2O PET scans of the heart allows for a non-invasive input function so the cerebral vascular reserve can be measured quantitatively.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Lisbeth Marner, MD, PhD; Phone Number: +4591171938; Email: lisbeth.marner@regionh.dk

Study Locations

• Denmark
  • Copenhagen NV
    • Copenhagen, Copenhagen NV, Denmark, 2400
      • Recruiting
      • Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Bispebjerg
      • Contact: Lisbeth Marner; Phone Number: +4591171938; Email: lisbeth.marner@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Recruited from Department of Neurology, and Department of Geriatric and Palliative Medicine at Bispebjerg Hospital, Copenhagen, Denmark.

Healthy subjects are recruited from internet advertisments.

Description

Inclusion Criteria:

• presumed Alzheimer's Disease (group 1)
• diagnosed with small vessel disease of the brain by MRI and presumed cognitive dysfunction (group 2)

Exclusion Criteria:

• major claustrophobia
• major psychiatric diseases
• other major somatic diseases
• allergy to diamox

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alzheimer Disease; patients with presumed Alzheimer disease and no known vascular, psychiatric or other major diseases age > 60 years	Diagnostic test: Cerebral [15O]H2O PET before and after diamox infusion; Cerebral [15O]H2O PET before and after diamox infusion
Small vessel disease; patients diagnosed with small vessel disease of the brain by MRI and presumed cognitive dysfunction and no other known psychiatric or other major diseases. age > 60 years	Diagnostic test: Cerebral [15O]H2O PET before and after diamox infusion; Cerebral [15O]H2O PET before and after diamox infusion
Healthy subjects; Age-matched subjects with no known vascular, psychiatric or other major diseases. age > 60 years	Diagnostic test: Cerebral [15O]H2O PET before and after diamox infusion; Cerebral [15O]H2O PET before and after diamox infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular reserve perfusion	Brain perfusion after diamox infusion (mL / min / 100 g tissue)	20 min after diamox infusion
Vascular reserve change	Change in Brain perfusion after diamox infusion (mL / min / 100 g tissue and %) compared to before diamox infusion	20 min after diamox infusion

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Anticipated): April 15, 2023
• Study Completion (Anticipated): April 15, 2023

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Positron-Emission Tomography; Perfusion
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Alzheimer Disease; Dementia, Vascular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: H-21076058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Data will be available at reasonable request following Danish laws on personal data regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No